Regaine for Women Regular Strength

Minoxidil 20 mg/ml (2% w/v).

Contains propylene glycol.

For full list of excipients see section 6.1.

Cutaneous Solution (to be applied to the scalp).

Regaine for Women Regular Strength is indicated for the treatment of alopecia androgenetica in women aged between 18 and 65.

Onset and degree of hair regrowth may be variable among users. Although trends in the data suggest that those users who are younger, whose hair has been thinning for a shorter period of time or who have a smaller area of thinning on the vertex are more likely to respond to Regaine for Women Regular Strength, individual responses cannot be predicted.

Women aged 18-65:

Hair and scalp should be thoroughly dry prior to topical application of Regaine for Women Regular Strength. A dose of 1 ml Regaine for Women Regular Strength cutaneous solution should be applied to the total affected areas of the scalp twice daily. The total dosage should not exceed 2 ml. If fingertips are used to facilitate drug application, hands should be washed afterwards.

It may take twice daily applications for four months or more before evidence of hair growth can be expected.

If hair re-growth occurs, twice daily applications of Regaine for Women Regular Strength are necessary for continued hair growth. Anecdotal reports indicate that re-grown hair may disappear three to four months after stopping Regaine for Women Regular Strength application and the balding process will continue.

Users should discontinue treatment if there is no improvement after one year.

The method of application varies according to the disposable applicator used:

Pump spray applicator: this is useful for large areas. Aim the pump at the centre of the bald area, press once and spread with fingertips over the entire bald area. Repeat for a total of 6 times to apply a dose of 1 ml. Avoid breathing spray mist.

Extended spray-tip applicator: this is useful for small areas, or under hair. The pump spray applicator must be in place in order to use this additional applicator. Use in the same way as the pump spray.

Rub-on applicator: squeeze the upright bottle once to fill the 1 ml chamber to the black line. Invert bottle, dab on scalp, and spread Regaine for Women Regular Strength over the entire bald area until chamber is empty.

Children and the Elderly

Not recommended. The safety and effectiveness of Regaine for Women Regular Strength in users aged under 18 or over 65 has not been established.

Regaine for Women Regular Strength is contra-indicated:

− in users with a history of sensitivity to minoxidil, ethanol, or propylene glycol

− in users with treated or untreated hypertension

− in users with any scalp abnormality (including psoriasis and sunburn)

− in users with a shaved scalp

− if occlusive dressings or other topical medical preparations are being used.

Before using Regaine for Women Regular Strength, the user should determine that the scalp is normal and healthy.

Minoxidil is only indicated for the treatment of alopecia androgenetica and should not be used in other types of hair loss for example when there is no family history of hair loss, hair loss is sudden and/or patchy, hair loss is due to childbirth or the reason for hair loss is unknown.

The patient should stop using Regaine for Women Regular Strength and see a doctor if hypotension is detected or if the patient is experiencing chest pain, rapid heart beat, faintness or dizziness, sudden unexplained weight gain, swollen hands or feet or persistent redness.

Patients with known cardiovascular disease or cardiac arrhythmia should contact a physician before using Regaine for Women Regular Strength.

Regaine for Women Regular Strength is for external use only. Do not apply to areas of the body other than the scalp.

Hands should be washed thoroughly after applying the solution. Inhalation of the spray mist should be avoided.

Regaine for Women Regular Strength contains ethanol (alcohol), which will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin and mucous membranes) the area should be bathed with large amounts of cool tap water.

Regaine for Women Regular Strength contains propylene glycol, which may cause skin irritation.

Some patients have experienced changes in hair colour and/or texture with use of Regaine for Women Regular Strength.

Patients should be advised to consult their doctor or pharmacist if they are concerned at any time during treatment with Regaine for Women Regular Strength.

Some consumers reported increased hair shedding upon initiation of therapy with Regaine for Women Regular Strength. This is most likely due to minoxidil's action of shifting hairs from the resting telogen phase to the growing anagen phase (old hairs fall out as new hairs grow in their place). This temporary increase in hair shedding generally occurs two to six weeks after beginning treatment and subsides within a couple of weeks. If shedding persists (>2 weeks), users should stop using Regaine for Women Regular Strength and consult their doctor.

Users should be aware that, whilst extensive use of Regaine for Women Regular Strength has not revealed evidence that sufficient minoxidil is absorbed to have systemic effects, greater absorption because of misuse, individual variability, unusual sensitivity or decreased integrity of the epidermal barrier caused by inflammation or disease processes in the skin (e.g. excoriations of the scalp, or scalp psoriasis) could lead, at least theoretically, to systemic effects.

Accidental ingestion may cause serious cardiac adverse events. Therefore this product has to be kept out of the reach of children.

Topical drugs, such as corticosteroids, tretinoin, dithranol or petrolatum, which alter the stratum corneum barrier, could result in increased absorption of minoxidil if applied concurrently. Although it has not been demonstrated clinically, there exists the theoretical possibility of absorbed minoxidil potentiating orthostatic hypotension caused by peripheral vasodilators.

There are no adequate and well controlled studies in pregnant women.

Animal studies have shown a risk to the foetus at exposure levels that are very high compared to those intended for human exposure (see section 5.3). The potential risk in humans is unknown.

Systemically absorbed minoxidil is secreted in human milk.

Regaine for Women Regular Strength should not be used during pregnancy or lactation.

Based on the pharmacodynamic and overall safety profile of minoxidil, it is not expected that Regaine for Women Regular Strength would interfere with the ability to drive or operate machinery.

In placebo controlled trials, the overall frequency of adverse events in females in all body system categories was approximately five times that of males.

Several thousand patients have used topical minoxidil in clinical trials where a comparison with an inactive solution was made. Dermatological reactions (e.g. irritation, itching) occurred in patients using both solutions. This has been explained by the presence of propylene glycol in both the active and inactive solution.

Data from 7 placebo controlled trials are available with a population of 1,197 males and females treated with topical minoxidil solution (2% and 5% combined) where adverse events were assessed. Additionally, adverse events reported in post-marketing are included.

The frequency of adverse reactions to topical minoxidil solution is defined using the following convention:

Very common (1/10); common (1/100, <1/10); uncommon (1/1,000, <1/100); rare (1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Users should stop using Regaine for Women Regular Strength if they experience chest-pain, tachycardia, faintness, dizziness, sudden unexplained weight gain, swollen hands or feet or persistent redness or irritation of the scalp.

Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine for Women Regular Strength are applied to larger surface areas of the body or areas other than the scalp.

Because of the concentration of minoxidil in Regaine for Women Regular Strength, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (5 ml of Regaine for Women Regular Strength contains 100 mg minoxidil; the maximum recommended adult dose for oral minoxidil administration in the treatment of hypertension). Signs and symptoms of minoxidil overdosage would primarily be cardiovascular effects associated with sodium and water retention, tachycardia and hypotension.

Treatment

Treatment of minoxidil overdosage should be symptomatic and supportive.

Pharmacotherapeutic group: other dermatologicals, ATC code: D11AX

Individual responses to Regaine for Women Regular Strength are variable and unpredictable.

The effect of Regaine for Women Regular Strength has been assessed in phase III clinical trials in women conducted over a 48 week treatment period.

In these studies Regaine for Women Regular Strength was compared to the product vehicle without the minoxidil active ingredient. The primary efficacy criterion was non-vellus hair count in a 1.0 cm² reference area of affected scalp. The mean changes observed in this parameter in these studies were significantly in favour of Regaine and were as follows:

Using non-vellus hair count as an efficacy criteria, Regaine for Women Regular Strength has also been shown to stabilise hair loss (defined as re-growth or no loss) in 88% of patients compared with 69% of patients who received vehicle in one trial following 48 weeks treatment and in 87% of patients compared with 73% of patients who received vehicle in a further trial following 32 weeks treatment.

Female patients' own evaluations in clinical studies have shown that hair growth was reported by approximately 60% of females after 8 months of Regaine for Women Regular Strength usage.

In addition, Regaine for Women Regular Strength has been shown to stabilise hair loss (shown as re-growth or no loss) in 4 out of 5 females as calculated from two clinical studies that showed stabilisation with 88 and 87% respectively while corresponding figures for vehicle were 69 and 74%.

The mechanism by which minoxidil stimulates hair growth is not fully understood, but minoxidil can reverse the hair loss process of androgenetic alopecia by the following means:

- increase the diameter of the hair shaft

- stimulate anagen growth

- prolong the anagen phase

- stimulate anagen recovery from the telogen phase

As a peripheral vasodilator minoxidil enhances microcirculation to hair follicles. The Vascular Endothelial Growth Factor (VEGF) is stimulated by minoxidil and VEGF is presumably responsible for the increased capillary fenestration, indicative of a high metabolic activity, observed during the anagen phase.

The failure to detect evidence of systemic effects during treatment with Regaine solution reflects the poor absorption of topically applied minoxidil from normal intact skin. Systemic absorption of minoxidil from topically applied solution ranges between 1% and 2% of the total applied dose.

In a study in males, the minoxidil serum concentration time curve (AUC) for the 2% solution averaged 7.54 ng·h/ml compared to a mean AUC of 35.1 ng·h/ml for the 2.5 mg oral formulation. The mean peak plasma concentration (C_max) for the topical solution was 1.25 ng/ml, compared to 18.5 ng/ml following the 2.5 mg oral dose.

There is some evidence from in vitro studies that minoxidil reversibly binds to human plasma proteins. However, since only 1 – 2% of topically applied minoxidil is absorbed, the extent of plasma protein binding occurring in vivo after topical application would be clinically insignificant. The volume of distribution of minoxidil after intravenous administration has been estimated at 70 litres.

Approximately 60% minoxidil absorbed after topical application is metabolised to minoxidil glucuronide, primarily in the liver. Minoxidil and its metabolites are excreted almost entirely in the urine, with a very minor degree of elimination via the faeces. Following cessation of dosing, approximately 95% of topically applied minoxidil will be eliminated within four days.

Preclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.

Cardiac effects of minoxidil in dogs are species-specific in terms of the low doses that cause profound haemodynamic effects and associated changes in the heart. Available data indicate that similar cardiac effects do not occur in humans treated topically or orally with minoxidil.

Mutagenicity

Minoxidil showed no evidence of mutagenic/genotoxic potential in a number of in vitro and in vivo assays.

Teratogenicity

Animal reproduction toxicity studies in rats and rabbits have shown signs of maternal toxicity and a risk to the foetus at exposure levels that are very high compared to those intended for human exposure (from 19 to 570-fold human exposure). A low, albeit remote, risk of foetal harm is possible in humans.

Fertility

Preclinical fertility studies in rats have shown minoxidil doses equal to or greater than 3 mg/kg/day (at least 21-fold human exposure) when administered orally and greater than 9 mg/kg/day (at least 64-fold human exposure) when administered subcutaneously were associated with reduced conception and implantation rates as well as a reduction in the number of live pups.

Propylene glycol

Ethanol

Water

Not applicable.

48 months

Regaine for Women Regular Strength is flammable. Do not store above 25°C.

HDPE bottle with spray-pump/dabbing applicator containing 60 ml of solution.

Pack size: 1 x 60 ml.

The solution is flammable. Do not use while smoking, or near any naked flame or strong heat source. Avoid exposure of the container and contents to naked flames during use, storage and disposal. Any unused product or waste material should be disposed of in accordance with local requirements.

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom

PL 15513/0149

7^th March 2005/27 Feb 2009

26 March 2012